Experimental Medications: New S1P Receptor Modulators

Ibudilast is a small-molecule targeted treatment that works on several sites in the brain to prevent macrophages, a type of immune cell, from migrating. This action suppresses production of cytokines, which are inflammatory molecules, and promotes regeneration of brain cells and the protective fiber that surrounds them. This treatment approach, or mechanism of action, differs from those of currently approved MS medications.77

The efficacy and safety of ibudilast in people with progressive forms of MS was assessed in the randomized, placebocontrolled Phase IIb SPRINT-MS trial. That 96-week study included 134 people with primary-progressive MS (PPMS) and 121 individuals with secondary-progressive MS (SPMS). Participants were randomized in a 1:1 ratio to receive ibudilast 100 mg daily or placebo. Based on MRI analyses, the study found that ibudilast reduced the rate of progression of whole brain atrophy (or shrinkage) by 48 percent compared to placebo, while being well tolerated and showing other benefits.77

Further analyses of the SPRINT-MS data sought to determine whether response to ibudilast differed among people with primaryprogressive MS, secondary-progressive MS without relapse, and secondary-progressive MS with relapse. After assessing the data, investigators reported that the overall effect of ibudilast on progression of brain atrophy in patients with progressive forms of MS appeared to result mainly from its impact on people with primary – rather than secondary – progressive MS.78

Subgroup analysis also found that – relative to placebo – the risk of confirmed disability progression was 46 percent lower among individuals with SPMS without relapse who received ibudilast, and 29 percent lower among treatment-group individuals with PPMS. That benefit, however, was not seen among those with SPMS who had suffered a relapse.79 These findings underscore the value of looking at the impact of medications in very specific patient populations in order to tailor treatments as closely as possible to a patient’s situation.